Abstract Psychopathy and substance abuse are severe, co-morbid clinical disorders associated with significant civil and criminal disruption. Significant strides have been made in understanding how substance abuse and psychopathy predict institutional behavior, criminal recidivism, and treatment outcome. However, little is understood in terms of the neurobiology of these two disorders and how they interact. Psychopathy and substance abuse are commonly associated with impaired decision-making in general, moral decision-making in particular. The purpose of the present proposal is to examine the common and unique neural systems associated with moral decision-making in psychopathy and substance abuse. Structural and functional imaging methods will be used to map the neural architecture associated with processing linguistic and picture based moral decision-making paradigms in male offenders stratified by psychopathy scores and substance abuse measures. This research will utilize a mobile MRI system that will be deployed to prison facilities to collect representative samples of offenders with psychopathy and substance abuse problems. Detailed analyses of this sample will enable us to delineate the neurocognitive systems associated with impaired moral decision-making in psychopathy and substance abuse. This research may have a direct impact on the development of cognitive behavioral therapies designed to treat these conditions.